Abstract
Granulysin is a newly described lytic molecule expressed by CTL and NK cells. Three mRNA (519, 520, and 522) and two protein products of 15 and 9 kDa are encoded by the granulysin gene. Stable transfectants overexpressing the predominate 520 mRNA were generated to determine the protein products originating from the translation of this message. A transfectant of the NK cell tumor YT overexpressed both 15 and 9 kDa proteins while a transfectant of the T cell tumor HuT78 produced mainly 15 kDa granulysin. Thus the 520 mRNA is sufficient for production of both 15 and 9 kDa granulysin. 9 kDa granulysin accumulated via post-translational processing of 15 kDa protein and was present intracellularly but not in the cell culture supernatant, indicating specific retention of the 9 kDa protein. An inhibitor of granule acidification, concanamycin A, blocked the processing of 15 kDa granulysin to the 9 kDa form. A deduced structural difference between the two forms of the protein and a decrease in lytic activity of 9 kDa granulysin at granule pH suggest two mechanisms by which a granulysin expressing cell is protected from autolysis during the biosynthesis of this potentially harmful molecule.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 413-422 |
| Number of pages | 10 |
| Journal | Molecular Immunology |
| Volume | 36 |
| Issue number | 7 |
| DOIs | |
| State | Published - May 1999 |
| Externally published | Yes |
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Keywords
- Biochemistry
- CTL
- Cytolytic granules
- NK cells
ASJC Scopus subject areas
- Molecular Biology
- Immunology
Cite this
Biosynthesis of granulysin, a novel cytolytic molecule. / Hanson, Dennis A.; Kaspar, Allan A.; Poulain, Francis R; Krensky, Alan M.
In: Molecular Immunology, Vol. 36, No. 7, 05.1999, p. 413-422.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Biosynthesis of granulysin, a novel cytolytic molecule
AU - Hanson, Dennis A.
AU - Kaspar, Allan A.
AU - Poulain, Francis R
AU - Krensky, Alan M.
PY - 1999/5
Y1 - 1999/5
N2 - Granulysin is a newly described lytic molecule expressed by CTL and NK cells. Three mRNA (519, 520, and 522) and two protein products of 15 and 9 kDa are encoded by the granulysin gene. Stable transfectants overexpressing the predominate 520 mRNA were generated to determine the protein products originating from the translation of this message. A transfectant of the NK cell tumor YT overexpressed both 15 and 9 kDa proteins while a transfectant of the T cell tumor HuT78 produced mainly 15 kDa granulysin. Thus the 520 mRNA is sufficient for production of both 15 and 9 kDa granulysin. 9 kDa granulysin accumulated via post-translational processing of 15 kDa protein and was present intracellularly but not in the cell culture supernatant, indicating specific retention of the 9 kDa protein. An inhibitor of granule acidification, concanamycin A, blocked the processing of 15 kDa granulysin to the 9 kDa form. A deduced structural difference between the two forms of the protein and a decrease in lytic activity of 9 kDa granulysin at granule pH suggest two mechanisms by which a granulysin expressing cell is protected from autolysis during the biosynthesis of this potentially harmful molecule.
AB - Granulysin is a newly described lytic molecule expressed by CTL and NK cells. Three mRNA (519, 520, and 522) and two protein products of 15 and 9 kDa are encoded by the granulysin gene. Stable transfectants overexpressing the predominate 520 mRNA were generated to determine the protein products originating from the translation of this message. A transfectant of the NK cell tumor YT overexpressed both 15 and 9 kDa proteins while a transfectant of the T cell tumor HuT78 produced mainly 15 kDa granulysin. Thus the 520 mRNA is sufficient for production of both 15 and 9 kDa granulysin. 9 kDa granulysin accumulated via post-translational processing of 15 kDa protein and was present intracellularly but not in the cell culture supernatant, indicating specific retention of the 9 kDa protein. An inhibitor of granule acidification, concanamycin A, blocked the processing of 15 kDa granulysin to the 9 kDa form. A deduced structural difference between the two forms of the protein and a decrease in lytic activity of 9 kDa granulysin at granule pH suggest two mechanisms by which a granulysin expressing cell is protected from autolysis during the biosynthesis of this potentially harmful molecule.
KW - Biochemistry
KW - CTL
KW - Cytolytic granules
KW - NK cells
UR - http://www.scopus.com/inward/record.url?scp=0032793656&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032793656&partnerID=8YFLogxK
U2 - 10.1016/S0161-5890(99)00063-2
DO - 10.1016/S0161-5890(99)00063-2
M3 - Article
VL - 36
SP - 413
EP - 422
JO - Molecular Immunology
JF - Molecular Immunology
SN - 0161-5890
IS - 7
ER -